Report of the Gynecologic Cancers Progress Review Group docx

Progress Review Groups Report of the Gynecologic Cancers Progress Review Group November 2001 Report of the Gynecologic Cancers Progress Review Group November 2001 From the Leadership It is a great pleasure to submit this Report of the Gynecologic Cancers Progress Review Group (GYN PRG) to the Acting Director and Advisory Committee to the Director of the National Cancer Institute (NCI). At the beginning of 2001, the GYN PRG accepted the charge of NCI Director Dr. Richard Klausner to develop a national plan for the next 5 years of gynecologic cancer research. The expertise of the GYN PRG members and the clinical, research, industrial and advocacy community participants of the GYN PRG Roundtable Meeting met that charge with this report. It reflects innovative research strategies that represent the next steps toward preventing, diagnosing and treating gynecologic cancers. We look forward to discussing these priorities with the leadership of the NCI. William J. Hoskins, M.D. Nicole Urban, Sc.D. Edward C. Trimble, M.D. PRG Co-Chair PRG Co-Chair PRG Executive Director Memorial Sloan-Kettering Fred Hutchinson Cancer National Cancer Institute Cancer Center Research Center We the undersigned members of the Gynecologic Cancers Progress Review Group concur with the enclosed report. William J. Hoskins, M.D. PRG Co-Chair Edward C. Trimble, M.D. PRG Executive Director Ruedi Aebersold, Ph.D. Garnet L. Anderson, Ph.D. Renzo Canetta, M.D. Mary B. Daly, M.D., Ph.D. Michael A. Friedman, M.D. Paul Goodfellow, Ph.D. Loretta Itri, M.D. Nicole Urban, Sc.D. PRG Co-Chair Ronald Alvarez, M.D. Michael J. Birrer, M.D., Ph.D. David Cella, Ph.D. Mary (Nora) Disis, M.D. David M. Gershenson, M.D. Hedvig Hricak, M.D., Ph.D. Beth Y. Karlan, M.D. Douglas R. Lowy, M.D. We the undersigned members of the Gynecologic Cancers Progress Review Group concur with the enclosed report. Cherie Nichols, M.B.A. Karl Podratz, M.D., Ph.D. Martha C. Romans, B.A. Branimir I. Sikic, M.D. Jane Weeks, M.D. Richard J. Zaino, M.D. Samuel Mok, Ph.D. Edward Partridge, M.D. Marcus E. Randall, M.D. Mary Jackson Scroggins, M.A. James Tate Thigpen, M.D. Stacey Young-McCaughan, R.N., Ph.D. Acknowledgments This report is the product of 11 months of intense work that drew on the combined expertise and efforts of many individuals. The Progress Review Group (PRG) particularly acknowledges the contributions of: • The many scientists, clinicians, and advocates across the country, who gave of their time and knowledge and were an integral part of making this report a successful document that should help advance research in gynecologic cancers. • Staff of the NCI Office of Science Planning and Assessment (OSPA), under the leadership of Cherie Nichols, who provided ongoing guidance and technical support throughout the PRG process—in particular, Deborah Duran and Anna T. Levy, who coordinated the PRG, as well as Kevin Callahan, James Corrigan, and Annabelle Uy. • A group of experienced science writers, who provided excellent writing support both during the Roundtable Meeting and the subsequent development of the PRG report: Deborah Shuman, Nancy Volkers, Randi Henderson, Alice Lium, Cheryl Pellerin, Barbara Shapiro, and Cheryl Ulmer. • Josette James, Audrey Thomas, and their colleagues at Palladian Partners, Inc., who provided excellent logistical support to the PRG. • David N. Louis, Co-Chair of the Brain Tumor Progress Review Group, for his presentation to Roundtable participants. Table of Contents Priorities of the Gynecologic Cancers Progress Review Group 1 Introduction 1 Background 1 Process 1 Overview of Priorities 3 Essential Research Priority 4 The Virtual Shared Specimen Resource 4 High-Impact Research Priorities 7 Molecular Profiling for Markers of Risk, Early Detection, and Treatment 7 Human Papillomavirus Vaccines 10 Quality of Life: Disparities Related to Care 12 Scientific Opportunities 14 Conclusion 16 Appendix A: About the National Cancer Institute’s Progress Review Groups 17 Appendix B: Gynecologic Cancers PRG Membership Roster 19 Appendix C: Gynecologic Cancers PRG Roundtable Participants Roster 21 Appendix D: Reports of the Gynecologic Cancers PRG Roundtable Breakout Groups 25 Health-Related Quality of Life and Survivorship 25 Clinical and Molecular Genetics 29 Defining Signatures of Cancer Cells, Genomics, Proteomics, and Informatics 32 Treatment and Drug Discovery 35 Immunology 40 Radiobiology 45 Laboratory and Clinical Models 54 Health Disparities, Communication, Education, and Quality of Care 57 Genes and Environment 60 Imaging 67 Tumor Biology, Hormone Receptors, Epithelial-Stromal Interactions, and Early Activation 70 Angiogenesis, Metastasis, and Growth Signaling 74 Early Detection, Screening, and Prevention 81 Treatment, Clinical Trials, Gene Therapy, Staging, and Surgery 87 Cervical Cancer 92 Endometrial Cancer 97 Ovarian Cancer 102 Priorities of the Gynecologic Cancers Progress Review Group Priorities of the Gynecologic Cancers Progress Review Group INTRODUCTION BACKGROUND Cervical, endometrial, and ovarian cancers represent 95 percent of gynecologic cancers and collectively rank fourth in both incidence and mortality among cancers that affect women. It is estimated that 80,300 women in the United States will be diagnosed with a gynecologic cancer (cancers of the cervix uteri, corpus uteri, and ovary) in 2001 and an estimated 26,300 will die of these diseases. Thus, gynecologic cancers will account for 14 percent of all solid tumors in women and 11 percent of deaths from them. Worldwide, gynecologic cancers account for an even larger share of cancer mortality in women. In non- industrialized countries, cervical cancer screening is minimal; consequently, this disease is a major cause of cancer deaths, second only to breast cancer in incidence and mortality. These three cancers have in common their origin in the organs of the female reproductive system, but they differ dramatically in most other ways. As with all solid tumors, the key to the control of gynecologic cancers lies in understanding their biology. If we can identify the genes, proteins, and environmental agents that drive their initiation and progression, we can make significant progress in improving outcomes for women at risk for these malignancies. We understand, and therefore control, cervical cancer best. Our recognition of precursor lesions in cervical cancer, and our use for nearly 50 years of the Pap test to detect them, has all but eradicated invasive cervical cancer in developed countries of the world. Our more recent discovery that infection by the human papillomavirus (HPV) is a necessary condition for the development of most if not all of cervical cancer provides an unprecedented opportunity. By developing vaccines against HPV infection and/or cervical cancer development among those exposed to HPV infection, there is the potential to control cervical cancer throughout the world. Although we do not understand endometrial cancer well, we do know the precursor lesion for the most common type of disease, and can usually detect and diagnose it early enough to treat it successfully. However, there is an aggressive form of endometrial cancer, type II, that, like ovarian cancer, is very poorly understood. Ovarian cancer, by far the most lethal of the gynecologic cancers in developed countries, has presented a challenge to researchers because it is not symptomatic until late in the disease process. Tumors are not easily identified using current methods of early detection. Research on biomarkers for early detection of ovarian cancer has resulted in at least one marker (CA-125) for ovarian cancer. CA-125 is currently being tested in randomized controlled trials along with an imaging method, transvaginal sonography, for early detection. In addition, recent applications of proteomic techniques have shown promise in identifying unique markers of ovarian cancer. Nevertheless, much work remains to be done in both ovarian and type II endometrial cancer if they are to be controlled within the next few decades. P ROCESS The Gynecologic Cancer Progress Review Group (GYN PRG) was charged with identifying and prioritizing areas of research to advance progress against these cancers. In this process, we attempted to maintain a global perspective, and our recommendations reflect priorities that will benefit women throughout the world. Priorities of the Gynecologic Cancers Progress Review Group 1 [...]... barriers to progress, drawing Report of the Gynecologic Cancers Progress Review Group on the reports of the scientific breakout groups Groups were to recommend four to six priorities for research in each specific disease type, as well as any recommendations relevant to all three disease sites Finally, the groups were asked to define an action plan to achieve the research goals The full reports of the 14... the cure of gynecologic cancer We encourage the reader to study in detail the individual reports of the 14 breakout groups and the 3 tumor-type groups, which are provided in Appendix C These individual reports expand further on the 10 priorities and offer additional direction for the research community The material in these reports represents the careful considerations of all participants at the Roundtable... Roundtable Report of the Gynecologic Cancers Progress Review Group Appendix A About the National Cancer Institute’s Progress Review Groups Appendix A: About the National Cancer Institute=s Progress Review Groups The National Cancer Institute (NCI) supports basic, clinical, and population-based research to elucidate the biology, etiology, early detection, prevention, and treatment of cancers of various... a VSSR for gynecologic cancer research • An advisory committee composed of leaders, including advocates, in Priorities of the Gynecologic Cancers Progress Review Group 5 gynecologic cancer research, such as members of the GYN PRG, should monitor and oversee the progress of the resource and the research it supports • Multiple institutions should collaborate in the development and use of the VSSR, with... address questions of quality of life and to devise interventions for cancer-related and treatment-related symptoms Report of the Gynecologic Cancers Progress Review Group Reduce or eliminate disparities in care Medical science has given us the means to effectively treat the majority of gynecologic cancers; currently, we cure approximately 72 percent of cervical cancers, 50 percent of ovarian cancers, and... understanding of mucosal immunity in the cervix • Prioritize the understanding of both endogenous factors (e.g., influences of hormones) and exogenous factors (e.g., smoking and other pathogens) and their role in influencing mucosal immune responses Priorities of the Gynecologic Cancers Progress Review Group 11 • Define the immunologic problems in the development of prophylactic versus therapeutic vaccines... realize the potential of the emerging technologies that require human Priorities of the Gynecologic Cancers Progress Review Group 3 tissue samples A cooperative effort of this kind, facilitated by the NCI, will speed progress in the type of research needed to control ovarian and endometrial cancer The time is right for such an initiative The NCI has already begun an important effort to work with the research... quality of life among women with gynecologic cancers? Recommended Actions 1 We propose large observational cohort studies of patients with newly and previously diagnosed gynecologic cancer These studies should do the following: Priorities of the Gynecologic Cancers Progress Review Group Investigate the impact of targeted interventions on patient-centered outcomes • Identify the influence of modifiable... ensure the adequate availability of banked specimens to meet the needs of the research community • Oversee a Specimen Allocation Committee, composed of investigators at the collection sites, which would approve applications for prospective collection of unique specimens to meet particular Report of the Gynecologic Cancers Progress Review Group scientific research objectives, as well as the use of stored... identified in this report If successful, the VSSR could become a model for a resource that covers tumor types beyond gynecologic cancers HIGH-IMPACT RESEARCH PRIORITIES Drawing on the discussions of Roundtable participants, the PRG leadership identified three areas of research: These areas were selected because of their importance to the science of gynecologic oncology in terms of both the state of the science . Progress Review Groups Report of the Gynecologic Cancers Progress Review Group November 2001 Report of the Gynecologic Cancers Progress Review. some of the needs of the These groups were asked to identify gaps in field. knowledge and barriers to progress, drawing 2 Report of the Gynecologic Cancers